PUBLICATION

Ewing sarcoma protein ewsr1 maintains mitotic integrity and proneural cell survival in the zebrafish embryo

Authors
Azuma, M., Embree, L.J., Sabaawy, H., and Hickstein, D.D.
ID
ZDB-PUB-071009-8
Date
2007
Source
PLoS One   2(10): e979 (Journal)
Registered Authors
Azuma, Mizuki, Embree, Lisa, Hickstein, Dennis D., Sabaawy, Hatem
Keywords
Embryos, Zebrafish, Apoptosis, Small interfering RNAs, Central nervous system, HeLa cells, Chromosomes, Somites
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Apoptosis
  • Cell Survival
  • Female
  • Gene Expression Regulation, Developmental*
  • Mitosis*
  • Models, Biological
  • Molecular Sequence Data
  • Neurons/metabolism*
  • Protein Binding
  • RNA-Binding Protein EWS/genetics
  • RNA-Binding Protein EWS/physiology*
  • RNA-Binding Proteins/genetics*
  • RNA-Binding Proteins/physiology*
  • Sequence Homology, Amino Acid
  • Zebrafish/embryology*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/physiology*
PubMed
17912356 Full text @ PLoS One
Abstract
BACKGROUND: The Ewing sarcoma breakpoint region 1 gene (EWSR1), also known as EWS, is fused to a number of different partner genes as a result of chromosomal translocation in diverse sarcomas. Despite the involvement of EWSR1 in these diverse sarcomas, the in vivo function of wild type EWSR1 remains unclear. PRINCIPAL FINDINGS: We identified two zebrafish EWSR1 orthologues, ewsr1a and ewsr1b, and demonstrate that both genes are expressed maternally, and are expressed ubiquitously throughout zebrafish embryonic development. Morpholino induced knockdown of both zebrafish ewsr1 genes led to mitotic defects with multipolar or otherwise abnormal mitotic spindles starting from the bud stage (10 hour post-fertilization (hpf)). The abnormalities in mitotic spindles were followed by p53-mediated apoptosis in the developing central nervous system (CNS) leading to a reduction in the number of proneural cells, disorganization of neuronal networks, and embryonic lethality by 5 days post-fertilization. siRNA silencing of EWSR1 in Hela cells resulted in mitotic defects accompanied by apoptotic cell death, indicating that the role of EWSR1 is conserved between zebrafish and human. CONCLUSIONS: Ewsr1 maintains mitotic integrity and proneural cell survival in early zebrafish development.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping